Somatomedin (SM), formerly called sulfation factor, is a growth hormone dependent plasma factor which acts directly on cartilage in vitro, whereas growth hormone does not. It causes stimulation of the incorporation of thymidine into DNA, uridine into RNA, leucine into protein, as well as sulfate into mucopolysaccharide. This project attempts to further elucidate the mechanisms of SM action. Somatomedin is removed from serum during incubation with viable rib cartilage or isolated chondrocytes. Attempts are being made to recover SM that has been bound to chondrocytes. If successful, we plan to vary the conditions of binding and release in hopes of infering the composition of the putative receptors. These techniques may also be useful for purification of SM. Present studies with Actinomycin D suggest that a major portion of SM stimulation of protein synthesis depends upon prior stimulation of RNA synthesis. Projected studies with other inhibitors should more precisely define the degree of interdependence of DNA, RNA, and protein synthesis.